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Objective: To categorize and quantify how states planned to use policy, systems, and environmental (PSE) change strategies in the Supplemental Nutrition Assistance Program-Education (SNAP-Ed)., Methods: Qualitative content analysis of SNAP-Ed annual plans from all 50 states, District of Columbia, Guam, and the US Virgin Islands between fiscal years 2014 and 2016., Results: Between 2014 and 2016, the percentage of states that included PSEs as a statewide goal increased from 25% to 47%, and the percentage that planned to implement at least 1 PSE increased from 56% to 98%. Among states that planned to implement PSEs in 2016, the 3 most common settings were places in which people learn (92%), live (90%), and work (83%)., Conclusions and Implications: The increased planned use of PSEs in SNAP-Ed was considerable and encouraging as PSEs are important to use in conjunction with direct education and social marketing to improve nutrition and prevent obesity., (Published by Elsevier Inc.)

Objectives: All Tanzanian abortion estimates rely on health facility data that do not take into account completely the incidence of abortion. This papers aims to estimate the lifetime incidence of induced abortion in Arusha, Tanzania via direct and double list-experiment methods using community data and evaluate outcomes and behaviors of women who had an abortion., Methods: From January to May 2018, a face-to-face interview survey was conducted on a representative sample of sexually active women (n = 3658) living in Arusha, Tanzania. Participants were selected in a three-stage random process and questions were asked about reproductive history, contraceptive use, and health seeking behaviors. A direct question and double list-experiment was used to estimate lifetime incidence of abortion., Results: Lifetime abortion incidence was 3% using the direct question compared to 7.7% using the double list-experiment method. However, post-estimation tests revealed a key study design violation thus invalidating list the experiment estimate. We find that 45% of women received their abortion outside the formal health care system, the most frequent method used was manyono pill (traditional medicine), and only 50% of women who experienced abortion complications sought treatment., Conclusions: We provide another example of the performance of list experiment in measuring abortion incidence. Nearly half of reported abortions took place outside of the formal health system highlighting the substantial underestimation while using facility data to measure abortion. Seeking health care for potential complications was low despite post-abortion care services being free and legal in Tanzania., Implications: Using administrative data to estimate lifetime incidence of abortion is inaccurate as we found half of our sample received abortions outside a health facility. Women should be encouraged to seek post-abortion care, when needed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To describe Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) site-level breastfeeding support practices and associations with breastfeeding outcomes., Design: Secondary analysis of WIC Infant and Toddler Feeding Practices Study-2, including data from interviews with caregivers of infants and interviews and surveys with staff from 27 WIC state agencies and 80 study sites., Participants: A total of 1,235 mothers of breastfed infants participating in the WIC Infant and Toddler Feeding Practices Study-2., Main Outcome Measure: Any and fully breastfeeding 2, 6, and 12 months postpartum., Analysis: Descriptive statistics described WIC site-level breastfeeding supports. Multilevel mixed modeling of breastfeeding at 2, 6, and 12 months, controlling for site- and participant-level characteristics., Results: Five WIC site-level supports were significantly and independently associated with any and fully breastfeeding: access to breastfeeding peer counselors, access to International Board Certified Lactation Consultants, postnatal home visits, allowing any WIC staff member to provide breast pump education, and having a policy not to provide formula during the first 30 days postpartum. Likelihood of any and fully breastfeeding increased with each additional site-level support present (odds ratio = 1.09, 95% confidence interval, 1.06-1.12; and odds ratio = 1.26, 95% confidence interval, 1.21-1.31, respectively)., Conclusions and Implications: Positive associations between site-level supports and breastfeeding at 2, 6, and 12 months were observed. Additional research is needed to understand how site-level supports interrelate and whether specific combinations are more effective, and to identify variations in implementation of breastfeeding supports., (Copyright © 2020 Society for Nutrition Education and Behavior. All rights reserved.)

Clinical evidence indicates that positive allosteric modulators (PAMs) of GABA A receptors have analgesic benefit in addition to efficacy in anxiety disorders. However, the utility of GABA A receptor PAMs as analgesics is compromised by the central nervous system side effects of non-selective potentiators. A selective potentiator of GABA A receptors associated with α2/3 subunits, KRM-II-81(5-(8-ethynyl-6-(pyridin-2-yl)-4H-benzo[f]imidazo[1,5-a][1,4]diazepin-3-yl)oxazole), has demonstrated anxiolytic, anticonvulsant, and antinociceptive effects in rodents with reduced motoric side effects. The present study evaluated the potential of KRM-II-81 as a novel analgesic. Oral administration of KRM-II-81 attenuated formalin-induced flinching; in contrast, diazepam was not active. KRM-II-81 attenuated nociceptive-associated behaviors engendered by chronic spinal nerve ligation (L5/L6). Diazepam decreased locomotion of rats at the dose tested in the formalin assay (10 mg/kg) whereas KRM-II-81 produced small decreases that were not dose-dependent (10-100 mg/kg). Plasma and brain levels of KRM-II-81 were used to demonstrate selectivity for α2/3- over α1-associated GABA A receptors and to define the degree of engagement of these receptors. Plasma and brain concentrations of KRM-II-81 were positively-associated with analgesic efficacy. GABA currents from isolated rat dorsal-root ganglion cultures were potentiated by KRM-II-81 with an ED 50 of 32 nM. Measures of respiratory depression were reduced by alprazolam whereas KRM-II-81 was either inactive or produced effects with lower potency and efficacy. These findings add to the growing body of data supporting the idea that α2/3-selective GABA A receptor PAMs will have efficacy and tolerability as pain medications including those for neuropathic pain. Given their predicted anxiolytic effects, α2/3-selective GABA A receptor PAMs offer an additional inroad into the management of pain., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Data from transgenic animals and novel pharmacological agents has realigned scientific scrutiny on the therapeutic potential of positive allosteric modulators (PAMs) of α2/3-containing GABA A receptors. Evidence for analgesic, anticonvulsant, and anxiolytic activity of α2/3-selective PAMs has been presented along with the clinical potential for a milder motor-impacting profile compared to non-selective GABA A receptor PAMs. A new series of α2/3-selective PAMs was recently introduced which has anxiolytic and anticonvulsant activity in rodent models. These molecules also produce efficacy against pain in multiple animal models. Additionally, co-morbid states of depression are prevalent among patients with pain and patients with anxiety. Compounds were shown to be selective for α2 and α3 constructs over α1 (except KRM-II-82), α4, α5, and α6 proteins in electrophysiological assays in transfected HEK-293T cells. Utilizing the forced-swim assay in mice that detects conventional and novel antidepressant drugs, we demonstrate for the first time that α2/3-selective PAMs are active in the forced-swim assay at anxiolytic-producing doses. In contrast, activity in a related model, the tail-suspension test, was not observed. Diazepam was not active in the forced-swim assay when given alone but produced an antidepressant-like effect in mice when given in conjunction with the α1-preferring antagonist, β-CCT, that attenuated the motor-impairing effects of diazepam. We conclude that these α2/3-selective PAMs deserve further scrutiny for their potential treatment of major depressive disorder. If effective, such a mechanism could add a beneficial antidepressant component to the anxiolytic, analgesic, and anticonvulsant spectrum of effects of these compounds., (Copyright © 2018. Published by Elsevier Inc.)

Positive allosteric modulators of GABA A receptors transduce a host of beneficial effects including anxiolytic actions. We have recently shown that bioavailability and anxiolytic-like activity can be improved by eliminating the ester functionality in imidazo[1,5-a][1,4]diazepines. In the present series of experiments, we further substantiate the value of heterocyle replacement of the ester for potential treatment of anxiety. None of three esters was active in a Vogel conflict test in rats that detects anxiolytic drugs like diazepam. Compounds 7 and 8, ester bioisosters, were selective for alpha 2 and 3 over alpha 1-containing GABA A receptors but also had modest efficacy at GABAA alpha 5-containing receptors. Compound 7 was efficacious and potent in this anxiolytic-detecting assay without affecting non-punished responding. The efficacies of the esters and of compound 7 were predicted from their efficacies as anticonvulsants against the GABA A antagonist pentylenetetrazole (PTZ). In contrast, the related structural analog, compound 8, did not produce anxiolytic-like effects in rats despite anticonvulsant efficacy. These data thus support the following conclusions: 1) ancillary pharmacological actions of compound 8 might be responsible for its lack of anxiolytic-like efficacy despite its efficacy as an anticonvulsant 2) esters of imidazo[1,5-a][1,4]diazepines do not demonstrate anxiolytic-like effects in rats due to their low bioavailability and 3) replacement of the ester function with suitable heterocycles markedly improves bioavailability and engenders molecules with the opportunity to have potent and efficacious effects in vivo that correspond to human anxiolytic actions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: We determined the diagnostic value of the trypsin inhibitor, uristatin, that is commonly found in urine and plasma in patients with infections or inflammations of any kind., Methods: We collected urine specimens from patients with infections of the urinary or upper respiratory tract and from healthy controls. We also collected blood from patients with a likely upper respiratory tract infection and healthy controls. A bacterial count of >10(5) organisms/ml in urine was considered to represent infection rather than contamination., Results: The uristatin dipstick test in urine showed acceptable negative predictive values (NPV of up to 93%) for patients without infection or inflammation. Here, the dipsticks could eliminate some urine cultures. For those with infection or inflammation, the positive predictive values (PPV) of the dipsticks were lower (up to 57%). Including the leukocyte esterase and nitrite values increased the PPV of the dipsticks for those with disease., Conclusions: The uristatin strip was more accurate than the leukocyte and nitrite dipsticks for predicting upper respiratory infections (URI) and C-reactive protein for those with infection or inflammation. The uristatin dipstick was able to detect both the bikunin and uristatin inhibitors.

Objective: To evaluate nutrient intakes, plasma phenylalanine (PHE) and tyrosine (TYR) concentrations, and physical growth of children with phenylketonuria undergoing nutrition management., Design: Children were fed three different medical foods during a one-year study. Subjects/setting Children were evaluated at baseline and every three months in metabolic clinics. Children's diets were managed at home. Statistical analyses Intakes of medical foods and nutrients, number of diaries with nutrients <67% and <100% of Recommended Dietary Intakes (RDI), and mean plasma PHE and TYR concentrations were compared among groups using two-way ANOVA. chi-squared test compared the percentage of plasma PHE and TYR concentrations in each group in specific categories. Height and body mass index were plotted against National Center for Health Statistics reference data; means were compared among groups. Tukey's test compared groups with significant treatment effects., Results: Mean intakes of nutrients, except energy by all groups and vitamin B-12 by the Periflex-fed group, met or exceeded RDIs. The oldest children tended to have the highest PHE intakes and plasma PHE concentrations. Mean length or height z score indicated normal linear growth. Mean body mass index z scores at study end suggested many children were overweight., Applications: Dietitians should prescribe adequate medical food and encourage children with phenylketonuria to ingest all prescribed daily. Linear growth of children, where mean protein equivalent intakes ranged from 113% to 129% of RDI, was normal, demonstrating the need for a protein intake greater than RDIs when an elemental diet is the primary protein source. Dietitians should prescribe and carefully monitor energy intake, physical activity, and weight.

Dedicated high-resolution small animal imaging systems have recently emerged as important new tools for cancer research. These new imaging systems permit researchers to noninvasively screen animals for mutations or pathologies and to monitor disease progression and response to therapy. One imaging modality, X-ray microcomputed tomography (microCT) shows promise as a cost-effective means for detecting and characterizing soft-tissue structures, skeletal abnormalities, and tumors in live animals. MicroCT systems provide high-resolution images (typically 50 microns or less), rapid data acquisition (typically 5 to 30 minutes), excellent sensitivity to skeletal tissue and good sensitivity to soft tissue, particularly when contrast-enhancing media are employed. The development of microCT technology for small animal imaging is reviewed, and key considerations for designing small animal microCT imaging protocols are summarized. Recent studies on mouse prostate, lung and bone tumor models are overviewed.